Selective expression rather than specific function of Txk and Itk regulate Th1 and Th2 responses.
Itk and Txk/Rlk are Tec family kinases expressed in T cells. Itk is expressed in both Th1 and Th2 cells. By contrast, Txk is preferentially expressed in Th1 cells. Although Itk is required for Th2 responses in vivo and Txk is suggested to regulate IFN-gamma expression and Th1 responses, it remains unclear whether these kinases have distinct roles in Th cell differentiation/function. We demonstrate here that Txk-null CD4(+) T cells are capable of producing both Th1 and Th2 cytokines similar to those produced by wild-type CD4(+) T cells. To further examine whether Itk and Txk play distinct roles in Th cell differentiation and function, we examined Itk-null mice carrying a transgene that expresses Txk at levels similar to the expression of Itk in Th2 cells. Using two Th2 model systems, allergic asthma and schistosome egg-induced lung granulomas, we found that the Txk transgene rescued Th2 cytokine production and all Th2 symptoms without notable enhancement of IFN-gamma expression. These results suggest that Txk is not a specific regulator of Th1 responses. Importantly, they suggest that Itk and Txk exert their effects on Th cell differentiation/function at the level of expression.
Sahu
Nisebita
N
Center for Molecular Immunology and Infectious Disease and Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, PA 16802, USA.
Venegas
Ana M
AM
Jankovic
Dragana
D
Mitzner
Wayne
W
Gomez-Rodriguez
Julio
J
Cannons
Jennifer L
JL
Sommers
Connie
C
Love
Paul
P
Sher
Alan
A
Schwartzberg
Pamela L
PL
August
Avery
A
D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000201:enzymology / Q000276:immunology / Q000469:parasitology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D012555:Schistosomiasis mansoni / Q000201:enzymology / Q000276:immunology; D018417:Th1 Cells / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D018418:Th2 Cells / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology
D000485:Allergens; D016207:Cytokines; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase